8JP2

Crystal structure of AKR1C1 in complex with DFV

8JP2 の概要

• エントリーDOI: 10.2210/pdb8jp2/pdb
• 分子名称: Aldo-keto reductase family 1 member C1, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 7-HYDROXY-2-(4-HYDROXY-PHENYL)-CHROMAN-4-ONE, ... (4 entities in total)
• 機能のキーワード: aldo-keto reductase 1c1;20alpha-hydroxysteroid dehydrogenase; complex;inhibitor;flavanone, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37838.99

構造登録者

Zheng, X.H.,Liu, H.,Yao, Z.Q.,Zhang, L.P. (登録日: 2023-06-10, 公開日: 2024-04-24)

主引用文献

Liu, H.,Yao, Z.,Sun, M.,Zhang, C.,Huang, Y.Y.,Luo, H.B.,Wu, D.,Zheng, X.
Inhibition of AKR1Cs by liquiritigenin and the structural basis.
Chem.Biol.Interact., 385:110654-110654, 2023

PubMed Abstract: In vivo and in vitro studies have confirmed that liquiritigenin (LQ), the primary active component of licorice, acts as an antitumor agent. However, how LQ diminishes or inhibits tumor growth is not fully understood. Here, we report the enzymatic inhibition of LQ and six other flavanone analogues towards AKR1Cs (AKR1C1, AKR1C2 and AKR1C3), which are involved in prostate cancer, breast cancer, and resistance of anticancer drugs. Crystallographic studies revealed AKR1C3 inhibition of LQ is related to its complementarity with the active site and the hydrogen bonds net in the catalytic site formed through C-OH, aided by its nonplanar and compact structure due to the saturation of the CC double bond. Comparison of the LQ conformations in the structures of AKR1C1 and AKR1C3 revealed the induced-fit conformation changes, which explains the lack of isoform selectivity of LQ. Our findings will be helpful for better understanding the antitumor effects of LQ on hormonally dependent cancers and the rational design of selective AKR1Cs inhibitors.

PubMed: 37666442
DOI: 10.1016/j.cbi.2023.110654

実験手法

X-RAY DIFFRACTION (1.8 Å)